COMPOSITION :
Nicardipine HCl Injection 10 mg/10 ml, each ml contains : Nicardipine HCl 1 mg.
DESCRIPTIONS :
Nicardipine HCl with Nicardipine HCl as active ingredient is available in injection 10 mg/10 ml.
INDICATIONS :
- Emergency treatment of acute hypertensive crisis during surgery.
- Hypertensive emergencies.
DOSAGE AND ADMINISTRATIONS :
- Emergency treatment of acute hypertensive crisis during surgery :
Nicardipine HCl injection is diluted with physiological saline to give 0.01% to 0.02% Nicardipine HCl (0.1 to 0.2 mg/ml) solution. The solution is administered by intravenous drip infusion at a starting rate of 2 to 10 mcg/kgBW/minute until the desired blood pressure value is reached and adjusted thereafter with monitoring to maintain blood pressure. For rapid blood pressure reduction, Nicardipine HCl injections may be administered intact at a dose of 10 to 30 mcg/kgBW by intravenous injection.
- Hypertensive emergencies :
Nicardipine HCl injections is diluted with isotonic Sodium chloride solution to give 0.01% to 0.02% Nicardipine HCl (0.1 to 0.2 mg/ml) solution. The solution is administered by intravenous drip infusion at a velocity of 0.5 to 6 mcg/kgBW/minute. The solution is administered at a dosing rate of 0.5 mcg/kgBW/minute until the desired blood pressure value is reached and adjusted thereafter with monitoring to maintain blood pressure.
Precautions concerning use
At the time of preparation :
- In IV drip infusion of this product, Nicardipine HCl may crystallize due to a high pH of the infusion fluid or for other reasons, therefore, careful attention should be paid to the possibility of such crystallization.
- Since the below mentioned injection solution have been found to date to be incompatible with this product, these solutions should not be combined with this product. Furosemide, Potassium canrenoate, Aminophylline, Bucladesine sodium, Amrinone, Lidocaine, Iohexol, Iopamidol, Tranexamic acid, Carbazochrome sodium sulfonate, Heparin sodium, Urokinase, Tisokinase, Altoplase, Phosphomycin, Cefotiam dihydrochloride, Cefuzonam sodium, Imipenem, Flomoxef sodium, Sodium bicarbonate.
- This product is supplied as a one-point-cut ampoule.
The cut point of the ampoule should be wiped with an alcohol swab before opening.
CONTRAINDICATIONS :
- Patients with suspected incomplete hemostasis following intracranial hemorrhage (Hemorrhage may be induced).
- Patients with elevated intracranial pressure at the acute stage of cerebral stroke (Intracranial pressure may be further elevated).
- Patients with medical history of hypersensitivity to Nicardipine HCl.
WARNINGS AND PRECAUTIONS :
- In patients with hypertensive emergencies, if it is necessary to control blood pressure after arrival at the desired blood pressure and if oral administration is feasible, replacement with oral drugs should be undertaken.
- In patients with hypertensive emergencies, it is reported that blood pressure may again increase on withdrawal of Nicardipine HCl. Therefore, the dose of Nicardipine HCl should be reduced gradually and blood pressure be controlled with caution after the product is withdrawn. Further, after replacement with oral drugs, patients should be cautioned against a re-increase in blood pressure.
- Preparation of the drip-injectable solutions : For IV drip infusion, a 0.01 – 0.02% Nicardipine HCl solution is prepared by adding the necessary volume of Nicardipine HCl injections to an infusion fluid which is suitable for concomitant use with Nicardipine HCl injections.
Refer to the table below :
| Volume of infusion fluid (ml) | Concentration of Nicardipine HCl solution to be prepared | ||
| About 0.01% | About 0.015% | About 0.02% | |
| Volume of Nicardipine HCl injections to be added (ml) | |||
| 100 | 12 | 18 | 24 |
| 250 | 30 | 45 | 60 |
| 500 | 60 | 90 | 120 |
- Careful administration (Nicardipine HCl injections should be administered with care in the following patients) :
- Patients with hepatic or renal dysfunction : Nicardipine HCl is metabolized in the liver. In general, acute hypotension in patients with severe renal dysfunction may induce renal hypofunction.
- Patients with aortic stenosis : The symptom may be exacerbated.
- Since the effects of Nicardipine HCl may differ in individual patients, this should be administered carefully under close monitoring of blood pressure and heart rate.
- If marked hypotension is caused by over dosage of Nicardipine HCl, administration should be discontinued. If rapid recovery of blood pressure is necessary, a vasopressor (Norepinephrine) should be administered.
- If any pain or redness appears at the injection site after long-term administration of Nicardipine HCl, the injection site should be changed.
- Others : In patients in the postsurgical monitoring period after open heart surgery, it is noted that some patients may develop circulatory failure and show symptoms of heart failure. Efficacy of Nicardipine HCl for such patients has not yet been established since there are only a few such cases (21 cases in total) to whom Nicardipine HCl has been administered.
- Use in pregnancy & lactation : Nicardipine HCl should only be used in pregnant women and women suspected of being pregnant provided that the expected therapeutic benefits are considered to outweigh the possible risk of treatment. In animal experiments where Nicardipine HCl was administered at a high dose during the terminal stage of pregnancy, an increase in fetal deaths, delivery disturbances, decrease in the body weight of offsprings and suppression of postnatal body weight gain were reported. The use of Nicardipine HCl is not recommended during lactation. If its use during lactation is necessary, the patient should discontinue breastfeeding. It has been reported in animal experiments that Nicardipine HCl is excreted into breast milk.
- Use in children : Safety of Nicardipine HCl in prematures, newborns, sucklings, infants and children have not been established.
- Use in the elderly : Since the elderly often have physiological hypofunction (liver, kidney, etc), it is advisable to start the treatment at a low dose (e.g. IV drip infusion at 0.5 mcg/kgBW/minute) and continue with careful monitoring.
DRUG INTERACTIONS :
Nicardipine HCl injections should be administered with care when co-administered with the following drugs :
| Drugs | Signs, symptoms and treatment | Mechanism and risk factors |
| HIV-protease inhibitors
Saquinavir, Ritonavir, etc |
AUC of Nicardipine HCl may be expectedly increased. | Due to competitive inhibition on cytochrome P450. |
| Other hypotensive drugs | Hypotensive effect may be enhanced. | Due to a pharmacological additive effect of both drugs. |
| β-blockers
Propranolol, etc |
In patients with congestive heart failure, an excessive decrease in blood pressure and a reduction in cardiac functions may appear.
Either of the drugs should be reduced or discontinued, if required. |
Due to a pharmacological additive effect.
|
| Fentanyl | During anesthesia with Fentanyl, hypotension occurs occasionally on the co-administration of Nicardipine HCl with β-blocker, reduction of dosage or discontinuation of either drug should be undertaken if necessary. | Mechanism of action is unknown. |
| Cimetidine | The effects of Nicardipine HCl may be enhanced and a decrease in blood pressure, tachycardia, etc may appear. The dosage of Nicardipine HCl should be reduced, if required. | Blood level is increased due to inhibition of the hepatic drug metabolizing enzyme P450 associated with metabolism of Ca antagonist. |
| Digoxin | The effects of Digoxin may be enhanced and toxic symptoms (nausea, vomiting, dizziness, bradycardia, arrhythmia, etc) may appear. This dosage of Nicardipine HCl should be reduced, if required. | Nicardipine HCl decreases clearance mainly in the kidneys to increase blood concentrations of Digoxin. |
| Immunosuppresant
Cyclosporin, Tacrolimus hydrate, etc |
The effects of immunosuppressants may be enhanced and toxic symptoms (especially renal dysfunction) may appear.
In addition, the effects of Nicardipine HCl may be enhanced and a decrease in blood pressure, tachycardia, etc, may appear. The dosage of immunosuppressant and Nicardipine HCl should be reduced, if required. |
Nicardipine HCl inhibits a drug metabolizing enzyme P450 in the liver competitively and the blood concentration of an immunosuppressant or Nicardipine HCl will be elevated. |
| Phenytoin |
|
|
| Rifampicin | The effects of Nicardipine HCl may be weakened. The dosage of Nicardipine HCl should be increased, if required. | Metabolism of Ca antagonists is accelerated because Rifampicin induces drug metabolizing enzyme in the liver. |
| Dantrolene sodium | Ventricular fibrillation and circulatory collapse were reported in animal experiments on other Calcium antagonists (such as Verapamil, etc). | Hypecalcemia is considered to occur. |
| Tandospirone citrate | Enhanced hypotensive effect was reported in animal experiments. | Tandospirone citrate has a central hypotensive effect and an additive hypotensive effect is exhibited. |
| Nitroglycerin | Atrioventricular block was reported in animal experiments. | Mechanism of action is unknown. |
| Muscle relaxants
Pancuronium bromide, Vecuronium bromide, etc |
The effect of the muscle relaxants may be enhanced. Patients should be carefully observed and if abnormalities occur, administration of both drugs should be reduced or discontinued. | Nicardipine HCl is thought to reduce the release of acetylcholine from presynaptic and postsynaptic nerve terminals at the neuromuscular junction and Calcium release from the sarcoplasmic reticulum of skeletal muscle, resulting in reduced muscle contraction. |
ADVERSE REACTIONS :
- Clinically significant adverse reactions :
- Paralytic ileus (unknown incidence) : Paralytic ileus may occur. If abnormal signs develop, administration should be discontinued and appropriate measures should be taken.
- Hypoxemia : Hypoxemia may occur infrequently. If abnormal signs develop, administration should be discontinued and appropriate measures should be taken.
- Anginal pain (cases in a foreign country; unknown incidence) : It is reported that patients treated with Nicardipine HCl injection developed anginal pain or experienced its exacerbation. If such signs develop, administration should be discontinued and appropriate measures should be taken.
- Thrombocytopenia (unknown incidence) : Thrombocytopenia may occur. Patients should be carefully observed and if abnormal signs develop, administration should be discontinued and appropriate measures should be taken.
- Hepatic function disorder and jaundice (unknown incidence) : Hepatic function disorder associated with elevation of AST (GOT), ALT (GPT) or γ-GTP and jaundice may occur. Patients should be carefully observed and if abnormal signs develop, administration should be discontinued and appropriate measures should be taken.
- Other adverse reactions :
| Other adverse reactions | Unknown incidence | |
| Cardiovascular | Tachycardia, palpitation, facial flush, generalized fatigability and ECG changes. | – |
| Hepatic | Hepatic dysfunction (elevation of GOT or GPT). | – |
| Renal | Elevation of BUN or creatinine. | – |
| Gastrointestinal | Nausea, vomiting, gagging. | – |
| Others | Headache, elevation of body temperature, decrease in urine volume, decrease in blood total cholesterol level, rigors, back pain, elevation of serum Potassium level. | Phlebitis |
PRESENTATION :
Nicardipine HCl Injection 10 mg/10 ml Box, 10 ampoules @ 10 ml Reg. No. GKL1502350743A1
STORAGE :
STORE BELOW 30°C, PROTECT FROM LIGHT
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
